The molecular bases underlying many human and animal physiological states (e.g., diseased and homeostatic states of various tissues) remain unknown. Nonetheless, it is well understood that these states result from interactions among the proteins and nucleic acids present in the cells of the relevant tissues. In the past, the complexity of biological systems overwhelmed the ability of practitioners to understand the molecular interactions giving rise to normal and abnormal physiological states. More recently, though, the techniques of molecular biology, transgenic and null mutant animal production, computational biology, and pharmacogenomics have enabled practitioners to discern the role and importance of individual genes and proteins in particular physiological states.
Knowledge of the sequences and other properties of genes (particularly including the portions of genes encoding proteins) and the proteins encoded thereby enables the practitioner to design and screen agents which will affect, prospectively or retrospectively, the physiological state of an animal tissue in a favorable way. Such knowledge also enables the practitioner, by detecting the levels of gene expression and protein production, to diagnose the current physiological state of a tissue or animal and to predict such physiological states in the future. This knowledge furthermore enables the practitioner to identify and design molecules which bind with the polynucleotides and proteins, in vitro, in vivo, or both.
Cadherins are a class of cell-surface adhesion molecules that mediate calcium-dependent cell-to-cell adhesion. Many cadherins exhibit homophilic adhesion; i.e. they bind with molecules of the same cadherin on a different cell. However, cadherins that bind specifically with other molecules have also been described (e.g. Telo et al., 1998, J. Biol. Chem. 273:17565-17572; Ludviksson et al., 1999 J. Immunol. 162:4975-4982). In addition to their binding capabilities, cadherins also exhibit transmembrane signaling and regulatable adhesion activity (e.g. Yap et al., 1997, 13:119-146; Gumbiner, 2000, J. Cell Biol. 148:399-403). Despite the fact that numerous cadherins and cadherin-like proteins have been described, many others have not yet been characterized. A family of cadherin-like proteins which the inventor believes to be novel is described herein.
Many secreted proteins, for example, cytokines and cytokine receptors, play a vital role in the regulation of cell growth, cell differentiation, and a variety of specific cellular responses. A number of medically useful proteins, including erythropoietin, granulocyte-macrophage colony stimulating factor, human growth hormone, and various interleukins, are secreted proteins. Thus, an important goal in the design and development of new therapies is the identification and characterization of secreted and transmembrane proteins and the genes which encode them.
Many secreted proteins are receptors which bind a ligand and transduce an intracellular signal, leading to a variety of cellular responses. The identification and characterization of such a receptor enables one to identify both the ligands which bind to the receptor and the intracellular molecules and signal transduction pathways associated with the receptor, permitting one to identify or design modulators of receptor activity, e.g., receptor agonists or antagonists and modulators of signal transduction.